•Related Small Molecules:

Biological Activity

Protocol

Technical Information

Purity & Documentation

References

Description

A-366 is a peptide-competitive inhibitor of G9a/GLP with an enzymatic IC50 of ~3 nM and >100-fold selectivity over other methyltransferases and other non-epigenetic targets.
IC50 value: 3 nM
Target: HMTase
in vitro: A-366 is a cell-active G9a/GLP small molecule inhibitor. The potency and selectivity of A-366 made it an ideal candidate to probe the cellular activities of G9a/GLP. A-366 reduced the total levels of H3K9me2 in a time and concentration dependent manner with a cellular EC50 of ~300 nM. A-366 has significantly less cytotoxic effects on the growth of tumor cell lines compared to other known G9a/GLP small molecule inhibitors despite equivalent cellular activity on methylation of H3K9me2. Additionally, the selectivity profile of A-366 has aided in the discovery of a potentially important role for G9a/GLP in maintenance of leukemia. Long term treatment of leukemia cell lines with A-366 results in differentiation and inhibition of growth
in vivo: Mice treated with A-366 administered via osmotic mini-pump at 30 mg/kg/day for two weeks showed no overt toxicity. Furthermore, treatment of a flank xenograft leukemia model with A-366 resulted in growth inhibition consistent with the profile of H3K9me2 reduction observed.